Varenicline (Compound I) is the international commonly accepted name for 7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine (which is also known as 5,8,14-triazatetracyclo[10.3.1.02,11.04,9]-hexadeca-2(11),3,5,7,9-pentaene), and has an empirical formula of C13H13N3 and a molecular weight of 211.27. Varenicline L-tartrate is a commercially marketed pharmaceutically active substance known to be useful for the treatment of smoking addiction.

Varenicline L-tartrate is a partial agonist selective for α4β2 nicotinic acetylcholine receptor subtypes. In the United States, varenicline L-tartrate is marketed under the name Chantix™ for the treatment of smoking cessation.
Varenicline base and its pharmaceutically acceptable acid addition salts are described in U.S. Pat. No. 6,410,550. In particular, Example 26 of U.S. Pat. No. 6,410,550 describes the preparation of varenicline base and its hydrochloride salt using 1-(4,5-dinitro-10-aza-tricyclo[6.3.1.02,7]dodeca-2,4,6-trien-10-yl)-2,2,2-trifluoroethanone as starting compound. In particular, the hydrochloride salt of varenicline described in this reference has been obtained after crystallization from methanol/diethyl ether (The present inventors have reproduced said crystallization, and the varenicline hydrochloride obtained has been denominated herein as Form II. See Comparative Example 1). In addition, Examples 1 and 2 of U.S. Pat. No. 6,787,549B2 describe the preparation of varenicline citrate in different forms (Forms A and B). Also, Examples 1 and 2 of U.S. Pat. No. 6,794,388B2 describe the preparation of varenicline succinate in different forms (i.e. an anhydrous form and a hydrate form). Further, Examples 1 to 4 of U.S. Pat. No. 6,890,927B2 describe the preparation of varenicline tartrate in different forms (Forms A, B, and C).
Different salt forms of the same pharmaceutically active moiety differ in their physical properties such as melting point, solubility, chemical reactivity, etc. These properties may appreciably influence pharmaceutical properties such as dissolution rate and bioavailability.
In addition, polymorphism, which is defined as the ability of a substance to crystallize in more than one crystal lattice arrangement, can also influence many aspects of solid state properties of a drug. Different crystal modifications of a substance may differ considerably from one another in many respects such as their solubility, dissolution rate and finally bioavailability.
There exists a need for salt forms, which in addition might be in crystalline form, of such material that have superior chemical and/or physical properties that are useful in drug delivery applications.
This application sets forth several novel salt forms of varenicline base. These salt forms have been prepared and characterized as described herein.